Background: Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date discussion of the hormonal and molecular signalling pathways implicated in sex differences in kidney health and disease.
Summary: Estrogen and progesterone have protective effects on renal blood flow, glomerular filtration rate and nephron ion and water reabsorptive processes, whereas testosterone tends to compromise these functions. The biological effects of estrogen appear to be the most important in reinforcing kidney function and protecting against kidney diseases in females. The actions of estrogen are myriad but all tend to bolster kidney physiology to maintain a steady-state and adaptable extracellular fluid volume (ECFV) and blood pressure. Estrogen safeguards ECFV homeostasis by stimulating renal epithelial sodium channel (ENaC) and water channel (AQP2) expression and transport function. Renal maintenance of ECFV within narrow physiological limits is a first-line of defense against hypertension and lowers the risk of cardiovascular disease in women. The estrogenic and XX chromosome basis for a female advantage are evident in a wide range of kidney diseases including acute kidney injury, chronic kidney disease, end-stage kidney disease, diabetic kidney disease, and polycystic kidney disease. The molecular mechanisms involve estrogen regulation of nephron ion and water transport, genetic immunogenic responses, activation of the protective arm of the renin angiotensin-aldosterone system and XX chromosome reinforcement of immune responses. Kidney disease can also predispose patients to cancer and women are protected in renal cancer with lower incidence, morbidity, and mortality than age-matched men with the disease.
Key messages: This review underscores the importance of incorporating sex-specific considerations into clinical practice and basic research to bridge the gap in understanding and addressing biological sex disparities in kidney disease and renal cancer.
背景:肾脏生理和疾病中存在性别差异,其基础是性激素雌激素、孕酮和睾酮的生物作用。摘要:雌激素和孕酮对肾血流量、肾小球滤过率、肾小球离子和水的重吸收过程具有保护作用,而睾酮则会损害这些功能。雌激素的生物效应似乎是加强女性肾功能和预防肾脏疾病的最重要因素。雌激素的作用多种多样,但都倾向于增强肾脏的生理功能,以维持稳态和适应性细胞外液容量(ECFV)和血压。雌激素通过刺激肾上皮钠通道(ENaC)和水通道(AQP2)的表达和转运功能来保障细胞外液容量的平衡。肾脏将 ECFV 维持在狭窄的生理范围内,是抵御高血压的第一道防线,可降低女性罹患心血管疾病的风险。在急性肾损伤、慢性肾病、终末期肾病、糖尿病肾病和多囊肾等多种肾脏疾病中,女性优势的雌激素和 XX 染色体基础显而易见。其分子机制涉及雌激素对肾小球离子和水转运的调节、遗传免疫反应、肾素血管紧张素-醛固酮系统保护臂的激活以及 XX 染色体对免疫反应的强化。肾脏疾病还可能使患者易患癌症,女性肾癌患者受到保护,其发病率、发病率和死亡率均低于年龄匹配的男性肾癌患者:本综述强调了将性别特异性考虑因素纳入临床实践和基础研究的重要性,以弥补在理解和解决肾脏疾病和肾癌生物学性别差异方面的差距。
{"title":"Sex Differences in Kidney Health and Disease.","authors":"Brian J Harvey, Diego Alvarez de la Rosa","doi":"10.1159/000541352","DOIUrl":"https://doi.org/10.1159/000541352","url":null,"abstract":"<p><strong>Background: </strong>Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date discussion of the hormonal and molecular signalling pathways implicated in sex differences in kidney health and disease.</p><p><strong>Summary: </strong>Estrogen and progesterone have protective effects on renal blood flow, glomerular filtration rate and nephron ion and water reabsorptive processes, whereas testosterone tends to compromise these functions. The biological effects of estrogen appear to be the most important in reinforcing kidney function and protecting against kidney diseases in females. The actions of estrogen are myriad but all tend to bolster kidney physiology to maintain a steady-state and adaptable extracellular fluid volume (ECFV) and blood pressure. Estrogen safeguards ECFV homeostasis by stimulating renal epithelial sodium channel (ENaC) and water channel (AQP2) expression and transport function. Renal maintenance of ECFV within narrow physiological limits is a first-line of defense against hypertension and lowers the risk of cardiovascular disease in women. The estrogenic and XX chromosome basis for a female advantage are evident in a wide range of kidney diseases including acute kidney injury, chronic kidney disease, end-stage kidney disease, diabetic kidney disease, and polycystic kidney disease. The molecular mechanisms involve estrogen regulation of nephron ion and water transport, genetic immunogenic responses, activation of the protective arm of the renin angiotensin-aldosterone system and XX chromosome reinforcement of immune responses. Kidney disease can also predispose patients to cancer and women are protected in renal cancer with lower incidence, morbidity, and mortality than age-matched men with the disease.</p><p><strong>Key messages: </strong>This review underscores the importance of incorporating sex-specific considerations into clinical practice and basic research to bridge the gap in understanding and addressing biological sex disparities in kidney disease and renal cancer.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myths, Realities and Pathways Forward -- A Patient's Thoughts on Person-Centred Care.","authors":"Bill Wang","doi":"10.1159/000541730","DOIUrl":"https://doi.org/10.1159/000541730","url":null,"abstract":"<p><p>No abstract was required?</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Yan, Min Liu, Di-Fei Duan, Lin-Jia Yan, Ling Li, Deng-Yan Ma
Introduction: Middle-aged and older individuals often face significant challenges in adopting digital health solutions, leading to a digital divide that hinders their ability to benefit from mobile health (mHealth) interventions. This study aims to investigate the specific requirements of middle-aged and older patients with chronic kidney disease (CKD) for self-management through mobile health applications (mHealth apps), using the Kano model.
Methods: A multicenter cross-sectional survey was conducted from April to September 2023 in five hospitals across Sichuan, Shandong, Guangdong, and Shaanxi provinces in China. The Kano model was employed to analyze participants' preferences regarding mHealth apps for self-management.
Results: Out of 359 participants (57.1% men, predominantly aged 45-54), the study identified essential and desirable features for mHealth apps. Essential attributes include comprehensive CKD information and robust privacy protection. Key to enhancing user satisfaction are features like symptom and medication management, access to medical insurance information, and app interface simplicity. Additional attractive features for increasing app appeal include diet management, exercise guidance, and customizable text size.
Conclusion: This study identifies critical mHealth app features for self-management in middle-aged and older CKD patients, emphasizing the importance of user-centric design. The findings provide valuable insights for app developers to create tailored solutions that cater to the specific needs of this demographic, potentially enhancing their self-management capabilities.
{"title":"Demand Analysis of Self-Management Mobile Health Applications for Middle-Aged and older Patients with Chronic Kidney Disease Based on the Kano Model.","authors":"Yu Yan, Min Liu, Di-Fei Duan, Lin-Jia Yan, Ling Li, Deng-Yan Ma","doi":"10.1159/000541729","DOIUrl":"https://doi.org/10.1159/000541729","url":null,"abstract":"<p><strong>Introduction: </strong>Middle-aged and older individuals often face significant challenges in adopting digital health solutions, leading to a digital divide that hinders their ability to benefit from mobile health (mHealth) interventions. This study aims to investigate the specific requirements of middle-aged and older patients with chronic kidney disease (CKD) for self-management through mobile health applications (mHealth apps), using the Kano model.</p><p><strong>Methods: </strong>A multicenter cross-sectional survey was conducted from April to September 2023 in five hospitals across Sichuan, Shandong, Guangdong, and Shaanxi provinces in China. The Kano model was employed to analyze participants' preferences regarding mHealth apps for self-management.</p><p><strong>Results: </strong>Out of 359 participants (57.1% men, predominantly aged 45-54), the study identified essential and desirable features for mHealth apps. Essential attributes include comprehensive CKD information and robust privacy protection. Key to enhancing user satisfaction are features like symptom and medication management, access to medical insurance information, and app interface simplicity. Additional attractive features for increasing app appeal include diet management, exercise guidance, and customizable text size.</p><p><strong>Conclusion: </strong>This study identifies critical mHealth app features for self-management in middle-aged and older CKD patients, emphasizing the importance of user-centric design. The findings provide valuable insights for app developers to create tailored solutions that cater to the specific needs of this demographic, potentially enhancing their self-management capabilities.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingjuan Yan, Ni Zhang, Li Quan, Wei Bin, Jing Xi, Caoshuai Dou, Zhiwen Liu, Yongfeng Gui, Liang-Hong Yin
Introduction: Sepsis is the leading contributor to acute kidney injury (AKI), responsible for 45% to 70% of AKI occurrences. Despite this, septic AKI is a highly multifactorial and complex condition, and our grasp of its pathogenesis is still not fully developed. Consequently, there remains a significant gap in effective diagnostic and therapeutic strategies for septic AKI.
Methods: In the in vitro experiments, BUMPT cells were exposed to lipopolysaccharides (LPS). In vivo experiments involved inducing sepsis in mice through administration of LPS injections. Additionally, in certain experiments, either a miR-455-5p mimic or an anti-miR-455-5p LAN was administered to the mice via injections into the tail vein. The mice were then sacrificed 24 hours following LPS administration for subsequent analysis.
Results: We observed a significant elevation in miR-455-5p levels within renal tubular cells following LPS-induced septic AKI. Our investigation revealed that NF-κB plays a crucial role in the upregulation of miR-455-5p. Inhibition of NF-κB using TPCA-1 prevented the rise in miR-455-5p levels in BUMPT cells (mouse proximal tubular cells from Boston University) cultured in vitro. ChIP assays confirmed that NF-κB directly interacts with the promoter region of the miR-455-5p gene in response to LPS treatment. Functionally, introducing miR-455-5p mimics intensified cell apoptosis, kidney damage, and the production of inflammatory cytokines, while silencing miR-455-5p had protective effects in septic mice. Notably, administering anti-miR-455-5p enhanced SOCS3 expression, whereas miR-455-5p mimics reduced SOCS3 levels following LPS exposure. Furthermore, our luciferase reporter assays demonstrated that SOCS3 is a direct target of miR-455-5p.
Conclusion: This study indicates a NF-κB/miR-455-5p/SOCS3 axis which can exacerbate kidney damage by enhancing renal inflammation. This process highlights potential therapeutic targets for managing septic AKI.
{"title":"NF-κB/miR-455-5p/SOCS3 axis aggravates sepsis induced acute kidney injury through promoting renal inflammation.","authors":"Mingjuan Yan, Ni Zhang, Li Quan, Wei Bin, Jing Xi, Caoshuai Dou, Zhiwen Liu, Yongfeng Gui, Liang-Hong Yin","doi":"10.1159/000541727","DOIUrl":"https://doi.org/10.1159/000541727","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is the leading contributor to acute kidney injury (AKI), responsible for 45% to 70% of AKI occurrences. Despite this, septic AKI is a highly multifactorial and complex condition, and our grasp of its pathogenesis is still not fully developed. Consequently, there remains a significant gap in effective diagnostic and therapeutic strategies for septic AKI.</p><p><strong>Methods: </strong>In the in vitro experiments, BUMPT cells were exposed to lipopolysaccharides (LPS). In vivo experiments involved inducing sepsis in mice through administration of LPS injections. Additionally, in certain experiments, either a miR-455-5p mimic or an anti-miR-455-5p LAN was administered to the mice via injections into the tail vein. The mice were then sacrificed 24 hours following LPS administration for subsequent analysis.</p><p><strong>Results: </strong>We observed a significant elevation in miR-455-5p levels within renal tubular cells following LPS-induced septic AKI. Our investigation revealed that NF-κB plays a crucial role in the upregulation of miR-455-5p. Inhibition of NF-κB using TPCA-1 prevented the rise in miR-455-5p levels in BUMPT cells (mouse proximal tubular cells from Boston University) cultured in vitro. ChIP assays confirmed that NF-κB directly interacts with the promoter region of the miR-455-5p gene in response to LPS treatment. Functionally, introducing miR-455-5p mimics intensified cell apoptosis, kidney damage, and the production of inflammatory cytokines, while silencing miR-455-5p had protective effects in septic mice. Notably, administering anti-miR-455-5p enhanced SOCS3 expression, whereas miR-455-5p mimics reduced SOCS3 levels following LPS exposure. Furthermore, our luciferase reporter assays demonstrated that SOCS3 is a direct target of miR-455-5p.</p><p><strong>Conclusion: </strong>This study indicates a NF-κB/miR-455-5p/SOCS3 axis which can exacerbate kidney damage by enhancing renal inflammation. This process highlights potential therapeutic targets for managing septic AKI.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Serious outbreaks related to Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) have been reported globally. In 2011, Germany experienced a significant outbreak of HUS caused by enteroaggregative Escherichia coli (EAEC) O104:H4 strain. Since then, no other outbreaks of this strain have been reported. This study aims to evaluate pediatric patients affected by the second documented worldwide outbreak of STEC-HUS (EAEC O104:H4 serotype) contaminating local drinking water.
Methods: Medical records of patients hospitalized in five pediatric intensive care units (PICU) diagnosed with STEC-HUS between July and September 2022 were evaluated retrospectively.
Results: Eighteen patients (14 girls, and 4 boys) were enrolled in the study. The median age was 7.4 [Intetquartile range (IQ) 1.3-17] years. Abdominal pain was the most common symptom (100%). The mean duration between symptom onset and development of STEC-HUS was 3 days (IQ 1-9). EAEC O104:H4 serotype was detected in the stool samples of eight patients. Neurological involvement was observed in three patients, cardiac involvement in two patients, and both in one patient. Two patients required respiratory support and dialysis was performed in 16 (88.8%) patients. Plasmapheresis was administered to two patients, and eculizumab was given to four. No mortality was reported during follow-up; the mean durations of PICU and hospital stays were 11.3 and 31.6 days, respectively.
Conclusion: Outbreaks of HUS can have severe implications on mortality and morbidity. However, timely diagnosis and implementation of appropriate supportive care, including dialysis, respiratory support, and suitable medical treatment for eligible patients, can lead to favorable outcomes.
{"title":"An Outbreak of Shiga Toxin-Positive Enteroaggregative Escherichia coli 0104:H4 Related Hemolytic Uremic Syndrome in Turkey: A Multicenter Study.","authors":"Merve Havan, Anar Gurbanov, Ersin Özkan, Hacer Uçmak, Fevzi Kahveci, Zeynelabidin Öztürk, Evrim Kargın Çakıcı, Emel Uyar, Emeksiz Serhat, Özlem Temel, Gürkan Bozan, Hüsne Tuba Halıcıoğlu, Hasan Fatih Çakmaklı, Songül Yılmaz, Belkis Levent, Halil Özdemir, Zeynep Ceren Karahan, Zeynep Birsin Özçakar, Tanıl Kendirli","doi":"10.1159/000541687","DOIUrl":"https://doi.org/10.1159/000541687","url":null,"abstract":"<p><strong>Introduction: </strong>Serious outbreaks related to Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) have been reported globally. In 2011, Germany experienced a significant outbreak of HUS caused by enteroaggregative Escherichia coli (EAEC) O104:H4 strain. Since then, no other outbreaks of this strain have been reported. This study aims to evaluate pediatric patients affected by the second documented worldwide outbreak of STEC-HUS (EAEC O104:H4 serotype) contaminating local drinking water.</p><p><strong>Methods: </strong>Medical records of patients hospitalized in five pediatric intensive care units (PICU) diagnosed with STEC-HUS between July and September 2022 were evaluated retrospectively.</p><p><strong>Results: </strong>Eighteen patients (14 girls, and 4 boys) were enrolled in the study. The median age was 7.4 [Intetquartile range (IQ) 1.3-17] years. Abdominal pain was the most common symptom (100%). The mean duration between symptom onset and development of STEC-HUS was 3 days (IQ 1-9). EAEC O104:H4 serotype was detected in the stool samples of eight patients. Neurological involvement was observed in three patients, cardiac involvement in two patients, and both in one patient. Two patients required respiratory support and dialysis was performed in 16 (88.8%) patients. Plasmapheresis was administered to two patients, and eculizumab was given to four. No mortality was reported during follow-up; the mean durations of PICU and hospital stays were 11.3 and 31.6 days, respectively.</p><p><strong>Conclusion: </strong>Outbreaks of HUS can have severe implications on mortality and morbidity. However, timely diagnosis and implementation of appropriate supportive care, including dialysis, respiratory support, and suitable medical treatment for eligible patients, can lead to favorable outcomes.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Brenner's Unforgettable Legacy: Transforming Medicine and Renal Science for Generations.","authors":"Giuseppe Remuzzi, David Warnock","doi":"10.1159/000541866","DOIUrl":"https://doi.org/10.1159/000541866","url":null,"abstract":"","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph Hunter Holthoff, Joseph L Alge, John M Arthur, Fatima Ayub, Wadhah Bin Homam, Michael G Janech, Sreelakshmi Ravula, Nithin Karakala
Introduction: Acute kidney injury is associated with adverse outcomes, including death and dialysis. The goal of this study was to identify prognostic biomarkers of Acute Kidney Injury (AKI) that could be used across multiple phenotypes of AKI, and across different species.
Methods: Liquid chromatography/tandem mass spectrometry analysis of urine samples from three species (human, rat, mouse) and four etiologies of acute kidney injury identified five potential biomarkers; of which two were validated, complement C3 and vitamin D binding protein, in a cohort of 157 patients that developed AKI following cardiothoracic surgery. We studied the relationship between the biomarker's concentration in the urine and the development of a composite primary endpoint (stage 3 acute kidney injury within 10 days or death within 30 days).
Results: Of the153 patients who developed acute kidney injury following cardiovascular surgery; 17 met the combined primary outcome. The median concentration of urine complement C3 adjusted to urine creatinine had the best predictive value and was significantly higher in the primary-outcome group than in the controls. Similarly, the median concentration of vitamin D binding protein was higher in the primary-outcome group.
Conclusions: The studies provide proof in principle that cross-species discovery analyses could be a valuable tool for identifying novel prognostic biomarkers in AKI. Urine complement C3 and vitamin D binding protein could be promising early predictors of adverse outcome in patients who develop AKI after cardiac surgery.
导言急性肾损伤与不良后果有关,包括死亡和透析。本研究的目的是确定急性肾损伤(AKI)的预后生物标志物,这些标志物可用于多种表型的 AKI 和不同物种:对三种物种(人、大鼠、小鼠)和四种急性肾损伤病因的尿液样本进行液相色谱/串联质谱分析,确定了五种潜在的生物标志物;其中补体C3和维生素D结合蛋白这两种生物标志物已在心胸外科手术后发生AKI的157名患者队列中得到验证。我们研究了尿液中生物标志物浓度与综合主要终点(10 天内急性肾损伤 3 期或 30 天内死亡)之间的关系:结果:在心血管手术后出现急性肾损伤的 153 名患者中,有 17 人达到了综合主要终点。根据尿肌酐调整后的尿补体 C3 中位浓度具有最佳预测价值,且主要结果组明显高于对照组。同样,初选结果组的维生素 D 结合蛋白浓度中位数也更高:这些研究从原则上证明了跨物种发现分析可以成为鉴定 AKI 中新型预后生物标志物的重要工具。尿补体C3和维生素D结合蛋白有望成为心脏手术后发生AKI患者不良预后的早期预测指标。
{"title":"Urinary complement C3 and vitamin D binding protein predict adverse outcomes in patients with acute kidney injury after cardiac surgery.","authors":"Joseph Hunter Holthoff, Joseph L Alge, John M Arthur, Fatima Ayub, Wadhah Bin Homam, Michael G Janech, Sreelakshmi Ravula, Nithin Karakala","doi":"10.1159/000540664","DOIUrl":"https://doi.org/10.1159/000540664","url":null,"abstract":"<p><strong>Introduction: </strong>Acute kidney injury is associated with adverse outcomes, including death and dialysis. The goal of this study was to identify prognostic biomarkers of Acute Kidney Injury (AKI) that could be used across multiple phenotypes of AKI, and across different species.</p><p><strong>Methods: </strong>Liquid chromatography/tandem mass spectrometry analysis of urine samples from three species (human, rat, mouse) and four etiologies of acute kidney injury identified five potential biomarkers; of which two were validated, complement C3 and vitamin D binding protein, in a cohort of 157 patients that developed AKI following cardiothoracic surgery. We studied the relationship between the biomarker's concentration in the urine and the development of a composite primary endpoint (stage 3 acute kidney injury within 10 days or death within 30 days).</p><p><strong>Results: </strong>Of the153 patients who developed acute kidney injury following cardiovascular surgery; 17 met the combined primary outcome. The median concentration of urine complement C3 adjusted to urine creatinine had the best predictive value and was significantly higher in the primary-outcome group than in the controls. Similarly, the median concentration of vitamin D binding protein was higher in the primary-outcome group.</p><p><strong>Conclusions: </strong>The studies provide proof in principle that cross-species discovery analyses could be a valuable tool for identifying novel prognostic biomarkers in AKI. Urine complement C3 and vitamin D binding protein could be promising early predictors of adverse outcome in patients who develop AKI after cardiac surgery.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reuben Roy, Maharajan Raman, Paul M Dark, Philip A Kalra, Darren Green
Introduction: Recommendations to move to a race free estimating equation for glomerular filtration rate have gained increasing prominence since 2021. We wished to determine the impact of any future adoption upon the CKD patient population of a large teaching hospital, with a population breakdown largely similar to that of England as a whole.
Methods: We compared four estimating equations (MDRD, CKD-EPI (2009), CKD-EPI (2021) and EKFC) using the Bland-Altman method. Bias and precision were calculated (in both figures and percentages) for all patients with CKD and specific subgroups determined by age, ethnic group, CKD stage and sex. CKD stage was assessed using all four equations.
Results: All equations studied had a positive bias in South Asian patients and a negative bias in Black patients compared to CKD-EPI (2021). Similarly, there was a positive bias in White patients across all equations studied. Comparing CKD-EPI (2009) and EKFC this positive bias increased as patients aged, the opposite was seen with MDRD. Between 10% and 28% of patients in our dataset changed their CKD staging depending upon estimating equation used.
Discussion: Our work confirms previous findings that the MDRD equation overestimates eGFR in South Asians and underestimates eGFR in Blacks. The alternative equations also demonstrated similar bias. This may, in part, explain the health inequalities seen in ethnic minority patients in the UK. Applying our findings to the UK CKD population as a whole would result in anywhere from 260,000 - 730,000 patients having their CKD stage reclassified, which in turn will impact secondary care services.
{"title":"Adoption of CKD-EPI (2021) for GFR estimation - implications for UK practice.","authors":"Reuben Roy, Maharajan Raman, Paul M Dark, Philip A Kalra, Darren Green","doi":"10.1159/000541689","DOIUrl":"https://doi.org/10.1159/000541689","url":null,"abstract":"<p><strong>Introduction: </strong>Recommendations to move to a race free estimating equation for glomerular filtration rate have gained increasing prominence since 2021. We wished to determine the impact of any future adoption upon the CKD patient population of a large teaching hospital, with a population breakdown largely similar to that of England as a whole.</p><p><strong>Methods: </strong>We compared four estimating equations (MDRD, CKD-EPI (2009), CKD-EPI (2021) and EKFC) using the Bland-Altman method. Bias and precision were calculated (in both figures and percentages) for all patients with CKD and specific subgroups determined by age, ethnic group, CKD stage and sex. CKD stage was assessed using all four equations.</p><p><strong>Results: </strong>All equations studied had a positive bias in South Asian patients and a negative bias in Black patients compared to CKD-EPI (2021). Similarly, there was a positive bias in White patients across all equations studied. Comparing CKD-EPI (2009) and EKFC this positive bias increased as patients aged, the opposite was seen with MDRD. Between 10% and 28% of patients in our dataset changed their CKD staging depending upon estimating equation used.</p><p><strong>Discussion: </strong>Our work confirms previous findings that the MDRD equation overestimates eGFR in South Asians and underestimates eGFR in Blacks. The alternative equations also demonstrated similar bias. This may, in part, explain the health inequalities seen in ethnic minority patients in the UK. Applying our findings to the UK CKD population as a whole would result in anywhere from 260,000 - 730,000 patients having their CKD stage reclassified, which in turn will impact secondary care services.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chien-Wen Yang, Juan Carlos Q Velez, Debbie L Cohen
Background: Hypertension (HTN) is a common side effect of tacrolimus (Tac), the first-line antirejection medication for kidney transplant recipients. The impact of immediate-release tacrolimus (Tac IR) dosed twice daily versus extended-release tacrolimus (Tac ER) dosed once daily on long-term blood pressure control in kidney transplant recipients remains understudied. This study aims to compare the use of Tac IR versus Tac ER in kidney transplant recipients and evaluate the effects of the different formulations on systolic blood pressure (SBP), diastolic blood pressure (DBP), and HTN crisis.
Methods: This retrospective cohort study at a single institution collected baseline characteristics, time-varying exposure to Tac IR versus Tac ER, SBP, DBP, HTN crisis, and confounders at each posttransplant visit. A marginal structural linear mixed-effects model was employed to analyze the longitudinal blood pressure control in kidney transplant recipients receiving Tac IR and Tac ER.
Results: The final analysis included 654 patients, with mean ages of 52.0 years for Tac IR and 50.3 years for Tac ER. Males constituted 56.7% in Tac IR and 55.0% in Tac ER. Notably, the black population had 2.44 times higher odds of receiving Tac ER after adjusting for the rest of the baseline characteristics. No difference was found between longitudinal SBP (p = 0.386, 95% CI: -1.00, 2.57) or DBP (p = 0.797, 95% CI: -1.38, 1.06).
Conclusion: Our study indicates that posttransplant patients taking Tac ER exhibit no difference in chronic SBP and DBP controls compared to Tac IR.
背景高血压(HTN)是肾移植受者一线抗排斥药物他克莫司(Tac)的常见副作用。在肾移植受者中,每天服用两次的速释他克莫司(Tac IR)与每天服用一次的缓释他克莫司(Tac ER)对长期血压控制的影响仍未得到充分研究。本研究旨在比较肾移植受者使用 Tac IR 和 Tac ER 的情况,并评估不同制剂对收缩压 (SBP)、舒张压 (DBP) 和高血压危机的影响。方法 该回顾性队列研究在一家机构进行,收集了移植后每次就诊时的基线特征、Tac IR 与 Tac ER 的时变暴露、SBP、DBP、HTN 危机和混杂因素。采用边际结构线性混合效应模型分析了接受 Tac IR 和 Tac ER 治疗的肾移植受者的纵向血压控制情况。结果 最终分析包括 654 名患者,Tac IR 患者的平均年龄为 52.0 岁,Tac ER 患者的平均年龄为 50.3 岁。男性在 Tac IR 中占 56.7%,在 Tac ER 中占 55.0%。值得注意的是,在调整了其他基线特征后,黑人接受 Tac ER 的几率要高出 2.44 倍。纵向 SBP(p=0.386,95% CI:-1.00,2.57)或 DBP(p=0.797,95% CI:-1.38,1.06)之间未发现差异。结论 我们的研究表明,与 Tac IR 相比,服用 Tac ER 的移植后患者在慢性 SBP 和 DBP 控制方面没有差异。
{"title":"Immediate-Release versus Extended-Release Tacrolimus: Comparing Blood Pressure Control in Kidney Transplant Recipients - A Retrospective Cohort Study.","authors":"Chien-Wen Yang, Juan Carlos Q Velez, Debbie L Cohen","doi":"10.1159/000541334","DOIUrl":"10.1159/000541334","url":null,"abstract":"<p><strong>Background: </strong>Hypertension (HTN) is a common side effect of tacrolimus (Tac), the first-line antirejection medication for kidney transplant recipients. The impact of immediate-release tacrolimus (Tac IR) dosed twice daily versus extended-release tacrolimus (Tac ER) dosed once daily on long-term blood pressure control in kidney transplant recipients remains understudied. This study aims to compare the use of Tac IR versus Tac ER in kidney transplant recipients and evaluate the effects of the different formulations on systolic blood pressure (SBP), diastolic blood pressure (DBP), and HTN crisis.</p><p><strong>Methods: </strong>This retrospective cohort study at a single institution collected baseline characteristics, time-varying exposure to Tac IR versus Tac ER, SBP, DBP, HTN crisis, and confounders at each posttransplant visit. A marginal structural linear mixed-effects model was employed to analyze the longitudinal blood pressure control in kidney transplant recipients receiving Tac IR and Tac ER.</p><p><strong>Results: </strong>The final analysis included 654 patients, with mean ages of 52.0 years for Tac IR and 50.3 years for Tac ER. Males constituted 56.7% in Tac IR and 55.0% in Tac ER. Notably, the black population had 2.44 times higher odds of receiving Tac ER after adjusting for the rest of the baseline characteristics. No difference was found between longitudinal SBP (p = 0.386, 95% CI: -1.00, 2.57) or DBP (p = 0.797, 95% CI: -1.38, 1.06).</p><p><strong>Conclusion: </strong>Our study indicates that posttransplant patients taking Tac ER exhibit no difference in chronic SBP and DBP controls compared to Tac IR.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miriam Rigoldi, Caterina Mele, Matteo Breno, Amantia Imeraj, Sara Gamba, Arrigo Schieppati, Erica Daina
Introduction: Lysinuric Protein Intolerance (LPI) is a multisystemic inborn error of metabolism with a variable clinical expressivity, that usually begins in childhood with growth failure and gastroenterological/neurological problems related to the altered urea cycle and later complications involving the renal, pulmonary and immuno-hematological systems.
Case report: We present the case of a 40-year-old woman suffering from chronic kidney disease in the context of a LPI, whose diagnosis was challenging because the signs of the disease were always blurred and the patient never manifested critical episodes typical of this multisystemic disease. In addition to renal disease, splenomegaly, thrombocytopenia, elevated lactate dehydrogenase (LDH), hyperferritinemia and hypertriglyceridemia were also present. A thorough investigation of the patient's food preferences revealed her spontaneous aversion to protein-containing foods and excessive drowsiness during the occurrence of infectious episodes or on the rare occasions of excessive protein intake, although without ever coming to medical attention. These nuanced signs led us to suspect an impairment of the urea cycle and ultimately allowed us to narrow down the diagnosis to LPI through biochemical and genetic investigations.
Conclusion: Nephrologists should consider LPI in the differential diagnosis, whenever a patient presents with mixed proteinuria, tubular dysfunction and/or chronic kidney failure of unknown origin. In these circumstances, we suggest looking for other signs such as growth failure, signs and symptoms ascribed to urea-cycle impairment, pulmonary involvement, hepatosplenomegaly and laboratory alterations such as pancytopenia, hyperferritinemia, lipid abnormalities, elevated LDH.
{"title":"Lysinuric Protein Intolerance: not only a disorder for pediatric nephrologists. Case report.","authors":"Miriam Rigoldi, Caterina Mele, Matteo Breno, Amantia Imeraj, Sara Gamba, Arrigo Schieppati, Erica Daina","doi":"10.1159/000541363","DOIUrl":"https://doi.org/10.1159/000541363","url":null,"abstract":"<p><strong>Introduction: </strong>Lysinuric Protein Intolerance (LPI) is a multisystemic inborn error of metabolism with a variable clinical expressivity, that usually begins in childhood with growth failure and gastroenterological/neurological problems related to the altered urea cycle and later complications involving the renal, pulmonary and immuno-hematological systems.</p><p><strong>Case report: </strong>We present the case of a 40-year-old woman suffering from chronic kidney disease in the context of a LPI, whose diagnosis was challenging because the signs of the disease were always blurred and the patient never manifested critical episodes typical of this multisystemic disease. In addition to renal disease, splenomegaly, thrombocytopenia, elevated lactate dehydrogenase (LDH), hyperferritinemia and hypertriglyceridemia were also present. A thorough investigation of the patient's food preferences revealed her spontaneous aversion to protein-containing foods and excessive drowsiness during the occurrence of infectious episodes or on the rare occasions of excessive protein intake, although without ever coming to medical attention. These nuanced signs led us to suspect an impairment of the urea cycle and ultimately allowed us to narrow down the diagnosis to LPI through biochemical and genetic investigations.</p><p><strong>Conclusion: </strong>Nephrologists should consider LPI in the differential diagnosis, whenever a patient presents with mixed proteinuria, tubular dysfunction and/or chronic kidney failure of unknown origin. In these circumstances, we suggest looking for other signs such as growth failure, signs and symptoms ascribed to urea-cycle impairment, pulmonary involvement, hepatosplenomegaly and laboratory alterations such as pancytopenia, hyperferritinemia, lipid abnormalities, elevated LDH.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}